Search Results (295)

Alcohol-associated hepatitis (AH) is the most severe clinical manifestation of alcohol-associated liver disease. Corticosteroids are the only disease-specific therapy shown to improve short-term survival. Currently, no non-invasive markers are available to predict patient response to corticosteroids or long-term survival in AH. This study investigates whether surface antigens on plasma extracellular vesicles (EVs), key mediators of intercellular communication, can reflect the underlying immune dysregulation in AH and serve as prognostic markers. Patients with AH were prospectively enrolled between 2020 and 2024. Blood samples were collected before corticosteroid initiation during the first 24 h of hospitalization. EVs were characterized using nanoparticle tracking analysis, cryo-electron microscopy, and flow cytometry. Interleukin-6 (IL-6), soluble (s)CD62p, Circulating Vascular Cell Adhesion Molecule-1 (sVCAM), tumor necrosis factor receptor superfamily member 1 (TNRFS1a), and Intercellular Adhesion Molecule 1 (ICAM-1) were quantified by ELISA. Key outcome variables included response to corticosteroids and mortality. A total of 46 patients with AH and 28 healthy donors (HD) were included. EV concentration was significantly higher in AH patients than in HD (9.3 × 10¹¹ [IQR 4–24] versus 2.4 × 10¹¹ [IQR 2–4], p = 0.03). Specific EV antigens were associated with key clinical outcomes: CD20 and CD2 levels differed between patients with or without infections (bacterial, viral, and fungal) developed during hospitalization; CD40 and CD146 were elevated in patients who developed acute kidney injury. EVs enriched in monocyte (CD14) and T-reg (CD25) markers were associated with plasma IL-6 levels, while endothelial markers CD105 and CD146 correlated with sVCAM and sCD62p. EVs enriched in platelet (CD49e) and endothelial (CD31) markers were associated with corticosteroid response, whereas EVs enriched with endothelial (CD105 and CD146) and B lymphocyte (CD19) markers were associated with mortality. Overall, EVs enriched in endothelial and monocyte markers may represent a candidate non-invasive tool for predicting corticosteroid response and mortality in AH, aiding risk stratification and early identification of non-responders for timely transplant evaluation. Full article

Objective: Although non-hepato-pancreato-biliary (non-HPB) cancer, such as gastric and colorectal cancer, may cause biliary obstruction, the efficacy of endoscopic transpapillary drainage remains unclear. We investigated the clinical outcomes of endoscopic transpapillary drainage for biliary obstruction due to non-HPB cancer. Methods: This was a two-center retrospective observation study. We evaluated the technical success, clinical success, recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and overall survival (OS). OS was determined using the Kaplan–Meier method, and the significance was tested using the log-rank test. Cox regression hazard models were performed to identify the independent association of clinical parameters with OS. Results: This study included 43 cases. The technical success was achieved in all cases (100%), and the clinical success was achieved in 35 cases (81%). The occurrence rate of RBO and non-RBO AEs were 33% and 12%, respectively. The median TRBO was 176 days. Systemic chemotherapy was introduced in 17 cases (40%) after biliary drainage, and cases with the introduction of systemic chemotherapy had a significantly longer OS. C-reactive protein <3.4 mg/dL and biliary obstruction due to lymph node metastasis were independently associated with the introduction of systemic chemotherapy. In survival analysis, serum albumin >3.1 g/dL and the introduction of systemic chemotherapy were significant and independent predictive factors for the prolongation of OS. Conclusions: The endoscopic transpapillary drainage for biliary obstruction due to non-HPB cancer can provide favorable outcomes with appropriate patient selection. Full article

Background/Objectives: Despite the long-standing history of liver transplantation (LT) in Spain, no multicenter study has reviewed national outcomes for LT in metastatic neuroendocrine tumors (NETs). In the current era of transplant oncology, auditing these results is essential to refine patient selection and improve long-term outcomes. Methods: This retrospective observational study analyzed data from 13 centers, including 91 patients who underwent LT for NET between 1995 and 2024. Patients were stratified into two groups: Milan IN (those meeting the Milan criteria) and Milan OUT (the remainder). Results: Recurrence occurred in 57.1% of cases, and overall mortality was 51.6%. Of the 91 patients, 71 (78.0%) were Milan IN and 20 (22.0%) were Milan OUT. Five-year overall survival was 71.0% in Milan IN and 58.0% in Milan OUT, with a statistically significant difference. The 5-year disease-free survival (DFS) rate was 58.8% in Milan IN and 36.3% in Milan OUT; this difference was not statistically significant. Conclusions: In conclusion, strict adherence to Milan criteria and incorporation of modern prognostic factors are critical to optimize long-term survival in LT for NET. While the overall outcomes in this historical cohort are modest, future improvements are expected through more rigorous selection and the potential use of bridging or downstaging therapies. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor—kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence–lipid feedback loops may represent a disease-modifying opportunity in MASLD progression. Full article

Background: Multimodal AI integration across genomics, radiomics, and pathomics is rapidly evolving in oncology, but evidence remains heterogeneous and unevenly distributed across modalities. Objective: To map empirical studies integrating two or more -omic modalities, summarize integration and validation approaches, and identify gaps informing future directions toward surgomics. Methods: We conducted a scoping review in accordance with PRISMA-ScR, searching PubMed, Ovid, Wiley Online Library, and Google Scholar for English-language studies published from January 2020 to 5 March 2025. We charted study characteristics, modalities combined, fusion strategies, AI model categories, validation approaches, and reported performance metrics as presented by the original studies. Results: From 184 records, 11 studies met inclusion criteria (n = 1078 total participants across reported studies), most focusing on radiomics–pathomics integration; fewer incorporated genomics, and tri-modal fusion was uncommon. Studies varied widely in clinical tasks, endpoints, preprocessing, and validation, limiting direct comparability. Conclusions: The mapped evidence indicates growing methodological activity in radiopathomics and cross-scale association modeling, while tri-modal pipelines and clinically deployable multimodal workflows remain underdeveloped. Surgomics is presented as a conceptual, staged roadmap informed by these gaps rather than a current clinical capability. Full article

The clinical management of Pancreatic Neuroendocrine Neoplasms (Pan-NENs) is complicated by the disease’s intrinsic variability, which creates significant hurdles for accurate risk profiling and the standardization of treatment protocols. Recently, Artificial Intelligence (AI) has offered a promising avenue to address these challenges. By integrating and processing high-dimensional multimodal datasets (encompassing clinical history, radiomics, and pathology), these computational tools can refine survival forecasts and support the development of personalized medicine. However, the transition from experimental success to routine clinical use is currently obstructed by reliance on limited, retrospective cohorts that lack external validation, alongside unresolved concerns regarding algorithmic transparency and ethical governance. This review evaluates the current landscape of AI-driven prognostic modeling for Pan-NENs and critically examines the pathway towards their reliable integration into clinical practice. Full article

Background: Hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) has a poor prognosis, and the benefits of neoadjuvant therapy are unclear. This systematic review and meta-analysis aim to evaluate the impact of neoadjuvant treatment (NAT) followed by surgery versus surgery alone on survival outcomes. Methods: A PRISMA-compliant systematic review was conducted by searching the OVID databases Embase, Medline, PubMed, and Scopus for English-language comparative studies of resectable HCC with PVTT, up to 23 January 2025. Two reviewers independently screened, extracted data, and assessed risk of bias (ROBINS-I/ROB2). Hazard ratios (HRs) for overall survival (OS) and recurrence-free survival (RFS) were pooled for meta-analysis. Results: Seven studies (2015–2024, five retrospective cohorts, one non-randomised comparative, one RCT) included 621 patients. The pooled analysis demonstrated that NAT followed by surgery was associated with a significantly improved OS (HR: 0.48, 95% CI: 0.295–0.67, p-value < 0.001, I² = 0.00) and improved RFS (HR: 0.4, 95% CI: 0.2–0.58, p-value < 0.001, I² = 0.00). Conclusions: For patients with HCC and an associated PVTT, neoadjuvant treatment before surgery significantly improves both overall and recurrence-free survival. These findings support a multimodal approach. Current evidence is largely non-randomised and HBV-endemic, warranting prospective validation in aetiologically diverse cohorts, including Western ones. Full article

Background: Cirrhosis represents the final common pathway of chronic liver injury, arising from diverse etiologies such as metabolic, viral, autoimmune, and alcohol-related liver diseases. Despite similar exposures, disease progression varies considerably among individuals, suggesting a genetic contribution to susceptibility and outcome. Objective: This narrative review examines how specific genetic variants influence the risk, progression, and phenotypic expression of cirrhosis. It provides a structured synthesis of established and emerging gene associations, emphasizing their biological mechanisms and potential clinical relevance. Methods: This narrative review synthesizes evidence from all major biomedical and scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar, as well as reference lists of relevant articles, covering literature published between 2005 and 2025 on genetic polymorphisms associated with cirrhosis and its etiological subtypes. Content: Variants are categorized into four mechanistic domains—metabolic regulation, immune modulation, liver enzyme activity, and ancestry-linked expression patterns—representing a novel integrative framework for understanding genetic risk in cirrhosis. Well-characterized variants such as PNPLA3, TM6SF2, HSD17B13, and MBOAT7, along with less commonly studied loci and chromosomal alterations, are discussed in relation to major etiologies, including MASLD/MASH, viral hepatitis, alcohol-related liver disease, and autoimmune conditions. Conclusions: Genetic insights into cirrhosis offer pathways toward early risk stratification and personalized disease management. While polygenic risk scores and multi-omic integration show promise, their clinical translation remains exploratory and requires further validation through large-scale prospective studies. Full article

Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45–85) years; mean body mass index (BMI) 26.6 kg/m²). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with overall survival outcomes that have improved only modestly in recent years. Careful preoperative evaluation is essential for defining resectability and planning surgery. Modern imaging modalities, including high-resolution, contrast-enhanced CT, MRI and endoscopic ultrasound, provide a detailed assessment of vascular involvement and allow accurate staging according to various international criteria and consensus statements. In borderline and locally advanced cases, neoadjuvant therapy can aid in downsizing the tumor and increasing the likelihood of achieving negative margin resection (R0), offering long-term survival along with quality of life. When vascular invasion limits resectability, venous resection and reconstruction may permit an R0 resection in patients with borderline resectable disease that is both technically operable and physiologically tolerable for the patient. Arterial resection, however, remains controversial and is rarely justified because of its limited perioperative and survival benefits. Arterial divestment has emerged as an interesting alternative, allowing tumor clearance while avoiding full arterial reconstruction. Vascular reconstructions can be achieved through venorrhapy, end-to-end anastomosis, or segmental replacement using either autologous or synthetic grafts. With the advances in neoadjuvant treatment, the appropriate selection of candidates for vascular resection significantly increases the resectability rate, offering long-term survival along with satisfactory quality of life. In this review, a detailed literature review is performed regarding the best strategies in the diagnosis and surgical management of patients with borderline resectable and locally advanced pancreatic cancer requiring vascular resection. Full article

Pain is a dominant symptom in acute pancreatitis, yet high-level evidence guiding optimal analgesic management in acute pancreatitis has been limited. Emerging evidence suggests a role of non-steroidal anti-inflammatory drugs, including cyclooxygenase-2 inhibitors, and opioids in the management of pain in acute pancreatitis patients. Based on a narrative review of the current literature, we provide an overview of available evidence, give an update on recent studies, and propose a treatment algorithm for pain management in acute pancreatitis, considering pharmacological and non-pharmacological modalities, patient comorbidities, and disease severity. Existing studies are generally limited by small sample sizes, heterogeneity in outcomes, unidimensional pain assessments, and a lack of understanding for the pathophysiology of pain in acute pancreatitis. Future trials should focus on multicentre collaboration, comprehensive pain evaluation, adequate sample sizes, and understanding the complex molecular mechanisms of acute pancreatitis pain. Full article

GC-MS oxylipin profiling of brown and red algal thalli was performed. Brown algae (Fucus distichus and Alaria esculenta) were collected from the Barents Sea coastline nearby Teriberka, Murmansk region, Kola Peninsula, Russia, while other brown and red algae were sourced from the Pacific coast of the Russian Far East. Triols and δ-ketols (epoxyalcohol synthase products) were found in most brown and red algae. Several Heterokontophyta and Rhodophyta species possessed α-ketols (products of allene oxide synthase) and related vic-diols. Plasmodiophorols and ectocarpins (hydroperoxide bicyclase (HPB) products) were found only in brown algae from the Ectocarpales, Fucales, and Laminariales orders, not in brown algae from the Desmarestiales or Dictyotales orders, or in any red algae. Therefore, plasmodiophorol A and other HPB products could be used as chemotaxonomic markers for the classification of the separate orders of algae within Heterokontophyta. The in vitro incubations of F. distichus thalli with linoleic and α-linolenic acid resulted in the formation of α-ketols and the hydroperoxide bicyclase product, plasmodiophorol A. Full article

Biohydrogen production can be derived from low-value lignocellulosic biomass; however, in many biohydrogen producing systems, xylose is utilized less efficiently than glucose, which limits overall substrate conversion. To address this issue, Fe/Mn-modified biochar was employed to enhance dark fermentation of glucose–xylose mixed sugars, and its performance was compared with other inoculum treatments. The biochar addition achieved a hydrogen yield of 2.57 ± 0.10 mol-H₂/mol-sugar, representing 14.6% enhancement over untreated controls, while enabling complete substrate utilization across varying xylose proportions. Biochar supplementation also reduced the lag phase by 24.4% and increased hydrogen productivity by 47.3% in mixed-sugar cultivation. Integrated analyses of the experimental data revealed the dual role of Fe/Mn-modified biochar in constructing conductive extracellular polymeric substance networks and directing metabolic flux toward high-yield butyrate pathways. This work establishes Fe/Mn-biochar as a multifunctional microbial engineering tool that alleviates carbon catabolite repression and promotes the enrichment of hydrogen-producing bacteria (HPB), thereby providing a practical and effective strategy for enhanced biohydrogen production from lignocellulosic biomass. Full article

Honeybee products (HBPs), including honey, bee pollen, bee bread, royal jelly, propolis, beeswax, and bee brood, are increasingly used in food, nutraceutical, and cosmetic contexts. Because of their natural origin, HBPs can provoke allergic reactions ranging from localised dermatitis to life-threatening, systemic anaphylaxis. As the use of bee products for health purposes grows in apitherapy (a branch of alternative medicine), raising public awareness of their potential risks is essential. This narrative review synthesises the clinical manifestations of HBP allergy, culprit allergens present in each product, immunological mechanisms, diagnostic approaches, at-risk populations, and knowledge gaps. The analysis of the available literature suggests that, although relatively rarely, HPB may trigger allergic reactions, including anaphylactic shock. The sensitisation mechanism may be associated with both primary sensitisation and cross-reactivity and can be classified into type I (IgE-mediated) and type IV (T-cell-mediated). However, bee bread appears less allergenic than other HBPs, potentially due to lactic fermentation that can degrade allergenic proteins. Severe reactions following intake of bee bread have not been reported to date. Management of HBP allergic reactions centres on avoiding the products, educating about the risks, and providing more precise product labelling, specifying the allergen content. Individuals with atopy and beekeepers are at heightened risk of developing anaphylaxis; therefore, they should be particularly aware of the potential dangerous consequences of HPB use. Further research is needed to clarify the mechanisms of HBP allergies and improve safety for all users. Full article

This review explores the evolving role of endoscopic ultrasound (EUS) in the diagnosis and management of liver diseases, with a particular focus on chronic liver disease, focal hepatic lesions, portal hypertension, and post-transplant anatomy. A comprehensive literature review of PubMed, MEDLINE, and Embase studies up to August 2025 was conducted to identify the latest evidence on EUS-guided procedures, comparing them with traditional techniques. In diagnostics, EUS-guided liver biopsy provides real-time visualisation and precise tissue sampling, achieving longer specimen lengths and better patient outcomes compared to traditional percutaneous and transjugular approaches. For portal hypertension assessment, EUS-guided portal pressure gradient measurement is a promising alternative to conventional methods, with validation studies demonstrating strong correlation with hepatic venous pressure gradient measurements. In therapeutic applications, EUS facilitates precise interventions including gastric variceal treatment through combined coil and glue injection, management of visceral arterial pseudoaneurysms, selective portal vein embolisation, and targeted tumour ablation. While some applications remain in developmental stages, studies support the safety and efficacy of EUS in improving diagnostic accuracy and expanding therapeutic options for liver diseases. Ongoing technological advances in needle design, imaging capabilities, and artificial intelligence integration are expected to further enhance the utility of EUS in hepatology. Full article